As world population increases as well as prolonged human lifetime span, needs, desires and demands for medical treatments are only elevating. In recent years, a new approach, Tissue Engineering, which utilizes living cell, is spotlighted. The ultimate goal of Tissue Engineering is to fabricate artificial tissue and organ for transplantation to human body. Artificial tissue is fabricated part of the body which expresses particular functionality when transplanted to human body. However, transplantation to human body requires number of approving process which comes with long span activities.
Aside from human transplantation, another promising application is to use engineered tissue as research specimen, which includes toxicity screening, drug effect judgement, pathology judgement, developmental research, etc. By fabricating engineered tissue with only human cells and using them for experimentation, it will be possible to reproduce or mimic in vivo environment of human body. This leads to higher drug discovery research, personalized medication diagnosis and development observations, etc.
Especially in the field of cancer, medication diagnosis and effect prediction is always difficult one. This technology may enable better prediction when text specimen is made with patient own cancer cells and tested number of different drugs ex-vivo, or outside of the body, prior to actual medications.
There are two types of cells, one is floating cell and another is adherent cell which required scaffold. Floating cell includes blood cells and immune system, and adherent cell are organ, skin and bone cells. Adherent cell shall not be able to survive in long period when floating in cell suspension, and it is necessary to let them adhere to any scaffold such as dish or gel and such so that they can survive and proliferate. When adherent cell is located in non-adherent environment, which means there are nothing to adhere to, cells seek for scaffold and start adhering each other and consequently forms large cell aggregate, which is three-dimensional cellular structure. This phenomenon is widely known and reported in non-patent articles 1˜6. Non-patent article 1 describes this cell aggregating phenomenon is known as old as 1960's. Especially non-patent article 6 clarifies the idea using cell aggregate as “Building Block” which indicates that diversified type of cell could be used.
Japanese patent document JP-P4122280 describes a method of fabricating tissue plug from only living cell with desired shape without support. In detail, this process uses a chamber which possess micro-pore only at the bottom which enable medium to pass through, and apply just enough mediums inside of chamber so that part of cell aggregate are exposed to air, use in excess of medium of total chamber volume for maturation of cellular structure.
Also, there are number of methods of making three-dimensional cellular structure. U.S. Pat. No. 8,852,932 describes dispensing method which dispenses cell aggregate onto plane surface from printer nozzle, whereas PCT publication WO2017/150366 A1 (PCT/JP2017/00729) shows a process needle array process which penetrates through Spheroids as needed. The needle array process use support consists of a number of needles mounted on base, which needles penetrate number of spheroids for alignment, and remove needles after the maturation to obtain 3D cellular structure. Furthermore, PCT publication WO2005/047496 shows process of making 3D Cellular structure by accumulating multiple plane cultured cell sheets which was made on permeable sheet.
The following non-patent literature is also related to subject matter disclosed herein:
PLOS ONE, Journal. Pone. 0136681, “Scaffold-Free Tubular Tissues Created by a Bio-3D printer Undergo Remolding and Endothelialization when Implanted in Rat Aortae,” Manabu Itoh et al, Sep. 1, 2015;
Gordon R, Goel N S, Steinberg M S, Wiseman L L. A rheological mechanism sufficient to explain the kinetics of cell sorting. J Theor Biol. 1972; 37:43-73. [PubMed: 4652421];
Jakab K, Damon B, Marga F, Doaga O, Mironov V, Kosztin I, Markwald R, Forgacs G. Relating cell and tissue mechanics: implications and applications. Dev. Dyn. 2008; 237:2438-2449. [PubMed: 1872 9216];
Jakab K, Neagu A, Mironov V, Markwald R R, Forgacs G. Engineering biological structures of prescribed shape using self-assembling multicellular systems. Proc Natl Acad Sci USA. 2004; 101:2864-2869. [PubMed: 14981244];
Perez-Pomares J M, Foty R A. Tissue fusion and cell sorting in embryonic development and disease: biomedical implications. Bioessays. 2006; 28:809-821. [PubMed: 16927301]; and
Organ printing: Tissue spheroids as building blocks” Biomaterials. Vladimir Mironov, Richard P. Visconti, Vladimir Kasynocv, Gabor Forgacs, Christopher J. Drake, and Roger R. Markwald, 2009 April; 30(12):2164-2174. doi:10.101016.